1. Field of the Invention
A chemically-structured delivery system for targeting liposomes containing medication to the tooth structure of the oral cavity.
2. Description of Prior Art
A general background for understanding the chemical process steps that go into making vesicles and liposomes is set forth clearly in a publication "Biochemistry" by Lubert Stryer, published by W. H. Freeman and Company, San Francisco, Calif., U.S.A., copyright 1981.
The repertoire of membrane lipids is extensive, and Stryer states they may even be bewildering, but they do possess a critical common structural theme in that membrane lipids contain both a hydrophilic and hydrophobic moiety.
A space-filling model of a typical lipid has a general shape roughly rectangular with two fatty acid chains approximately parallel to one another and a hydrophilic moiety pointing in the opposite direction.
It is common practice to use a short hand illustration which has been adopted to represent these membrane lipids. The hydrophilic unit called the polar head group is represented by a circle and the hydrocarbon tails are represented by lines which may be straight or wavy.
The polar head groups have affinity for water and the hydrocarbon tails avoid water and seek lipid media. A bi-molecular sheet, known also as a lipid bi-layer, is the favored structure for most phospholipids and glycolipids in aqueous media.
The structure of a bi-molecular sheet is inherent in the structure of lipid molecules. Their formation is a rapid and spontaneous process in water. Hydrophobic interaction is the major driving force for the formation of lipid bi-layers. It is important to the final construction of a targeted liposome that there are van der Waals attactive forces between the hydrocarbon tails. These van der Waals forces favor close packing of the hydrocarbon tails, and also will accept the hydrocarbon moiety of target molecules from an aqueous solution.
Clustering of bipolar lipids is favored by the van der Waals attractive forces with the significant biological consequence that they will tend to close on themselves so that there are no ends with exposed hydrocarbon chains and therefore result in the formation of a compartment which is normally self sealing because a hole in a bi-layer is energetically unfavorable.
However, if one of the lipid components of such a closed compartment has one R-group missing, there will be a fault dislocation which defeats the self sealing behavior and allows the contents of the liposome to leak from the inner aqueous compartment.
Therefore, as explained in the prior art and particularly in the Stryer publication supra, liposomes are aqueous compartments enclosed by a lipid bi-layer. They can be formed by suspending a suitable lipid, such as phosphatidyl choline in an aqueous medium. This mixture is then sonicated, which is an agitation by high frequency sound waves, to give a dispersion of closed liposomes that are quite uniform in size. There are other methods of forming such liposomes, and one specific recommended procedure is set forth in the specification hereinafter.
Molecules, such as sodium fluoride for dental therapy, can be trapped in the aqueous compartment of liposomes by forming them in the presence of these substances. For example, if liposomes as small as 500 .ANG. in diameter are formed in a 0.1M glycine solution, Stryer states that about 2000 molecules of glycine will be trapped in each inner aqueous compartment. This manner of packaging oral cavity enhancement chemicals is the first step of the present invention.
The biochemistry of the polyphosphoinositides and the diphosphonates as noted in the scientific literature demonstrates that these molecules are capable of participating in chemical reactions that result in the formation of exceptionally strong coordination complexes with the calcium ions of the hydroxyapatite crystal over a very broad pH range.